Sirolimus as Secondary Therapy in Chronic Graft-Versus-Host Disease Not Responding To Prior Treatment
2017년 5월 23일 업데이트: Paul Carpenter, Fred Hutchinson Cancer Center
A Phase II Clinical Trial to Evaluate the Safety and Efficacy of Sirolimus for Secondary Treatment of Chronic Graft-versus-Host Disease
This phase II trial studies the side effects and how well sirolimus works as secondary therapy in treating patients with chronic graft-versus-host disease (GVHD) that did not respond to prior treatment.
Sirolimus may be an effective treatment for chronic GVHD
연구 개요
상세 설명
PRIMARY OBJECTIVES:
I. To assess the safety of sirolimus administered at a dose which provides steady-state, whole blood trough levels of 5-10 ng/mL in patients with chronic GVHD.
II. To determine whether administration of sirolimus provides benefit for patients with chronic GVHD that has not responded adequately to previous systemic treatment.
OUTLINE:
Patients receive sirolimus orally (PO) once daily (QD). Patients continue to receive prednisone and cyclosporine or tacrolimus at the discretion of the managing physician.
After completion of study treatment, patients are followed up periodically.
연구 유형
중재적
등록 (실제)
44
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Washington
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Seattle, Washington, 미국, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
- 어린이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
Biopsy-confirmed diagnosis of clinical extensive chronic GVHD with inadequate response to previous treatment and where secondary systemic therapy is indicated because of
- Clinical progression of signs and symptoms of chronic GVHD in a previously involved organ, or
- Development of signs and symptoms of chronic GVHD in a previously uninvolved organ, or
- Absence of improvement after 3 months of primary treatment, or
- Continued need for treatment with prednisone at doses >= 1.0 mg/kg/day for more than 2 months, without qualification for type of donor, graft or conditioning regimen
- Patient or guardian able and willing to provide informed consent
- Stated willingness to use contraception in women of child-bearing potential (Food and Drug Administration [FDA] requirement)
- Stated willingness of the patient to comply with study procedures and reporting requirements
- Stated willingness of the physician most involved in management of chronic GVHD (the "managing physician,") to comply with study procedures and reporting requirements
Exclusion Criteria:
- Fungal or viral infection with no radiographic evidence of improvement during continued appropriate antimicrobial therapy
- Cytomegalovirus (CMV) antigenemia unresponsive to antiviral therapy
- Active disseminated varicella zoster virus (VZV) infection with persistent non-crusted lesions
- Inability to tolerate oral medications
- Absolute neutrophil count (ANC) < 1500/uL
- Platelet count < 50,000/uL
- Persistent or recurrent malignancy, including histopathologic evidence of myeloma or lymphoma; patients with breakpoint cluster region-abelson (bcr/abl) detected by polymerase chain reaction (PCR) assay as the only evidence of persistent chronic myeloid leukemia may be enrolled
- Pregnancy
- Known history of hypersensitivity to sirolimus
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 지지 요법
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Sirolimus
Study participants receive sirolimus added once daily to their baseline combination therapy of prednisone plus either cyclosporine or tacrolimus at the discretion of the managing physician.
Treatment other than cyclosporine (or tacrolimus) and prednisone must be discontinued when administration of sirolimus is started.
Topical therapy, including psoralen and UVA irradiation (PUVA), glucocorticoid creams, topical tacrolimus, oral beclomethasone, topical azathioprine and ophthalmic glucocorticoids may be given at the discretion of the managing physician in consultation with the transplant center.
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주어진 PO
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Number of Participants Experiencing Treatment Success
기간: Approximately 7 years
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Defined as the absence of any immunosuppressive treatment, including sirolimus, with resolution of all reversible manifestations of chronic GVHD and no additional systemic therapy.
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Approximately 7 years
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Number of Participants Experiencing Treatment Failure
기간: Approximately 7 years
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Defined as the initiation of additional systemic therapy, development of bronchiolitis obliterans, or death from causes other than recurrent malignancy during primary treatment for chronic GVHD, whichever occurs first.
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Approximately 7 years
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Number of Participants Needing Additional Systemic Therapy
기간: Approximately 7 years
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Includes any intervention intended to control chronic GVHD through an immunosuppressive effect from oral or parenteral administration of any systemic medication not originally given under auspices of this protocol.
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Approximately 7 years
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Number of Participants With Recurrent Malignancy
기간: Approximately 7 years
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Defined as clinical or histopathologic evidence demonstrating the presence of any malignancy considered as the indication for transplant.
Recurrent malignancy will also be defined as any post-transplant intervention not routinely used to prevent the development of overt recurrence, prompted by laboratory evidence of persisting malignant cells but without clinical or histopathologic evidence of recurrence.
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Approximately 7 years
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity
기간: Approximately 7 years
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Approximately 7 years
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Proportion With Infections Categorized by Organism
기간: Approximately 7 years
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Approximately 7 years
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Secondary Malignancies
기간: Up to 7 years
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Proportion of participants who developed at least one secondary malignancy by 7 years
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Up to 7 years
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Duration of Treatment With Prednisone
기간: Approximately 7 years
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Approximately 7 years
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Probability of Survival Without Recurrent Malignancy
기간: Approximately 7 years
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Kaplan-Meier estimate assessed at 7 years for probability of survival without recurrent malignancy.
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Approximately 7 years
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Probability of Overall Survival
기간: Approximately 7 years
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Kaplan-Meier estimate assessed at 7 years
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Approximately 7 years
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Probability of Cumulative Incidence of Death Without Recurrent Malignancy
기간: Approximately 7 years
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Analyzed with recurrent malignancy as a competing risk factor.
Assessed at 7 years.
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Approximately 7 years
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Probability of Cumulative Incidence of Recurrent Malignancy
기간: Approximately 7 years
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Analyzed with death as a competing risk factor.
Assessed at 7 years.
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Approximately 7 years
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2002년 4월 1일
기본 완료 (실제)
2009년 7월 1일
연구 완료 (실제)
2010년 6월 10일
연구 등록 날짜
최초 제출
2004년 3월 8일
QC 기준을 충족하는 최초 제출
2004년 3월 9일
처음 게시됨 (추정)
2004년 3월 10일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2017년 6월 20일
QC 기준을 충족하는 마지막 업데이트 제출
2017년 5월 23일
마지막으로 확인됨
2017년 5월 1일
추가 정보
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